The cytoplasmic domain of anthrax toxin receptor 1 affects binding of the protective antigen.
The protective antigen (PA) component of anthrax toxin binds the I domain of the receptor ANTXR1. Integrin I domains convert between open and closed conformations that bind ligand with high and low affinities, respectively; this process is regulated by signaling from the cytoplasmic domains. To assess whether intracellular signals might influence the interaction between ANTXR1 and PA, we compared two splice variants of ANTXR1 that differ only in their cytoplasmic domains. We found that cells expressing ANTXR1 splice variant 1 (ANTXR1-sv1) bound markedly less PA than did cells expressing a similar level of the shorter splice variant ANTXR1-sv2. ANTXR1-sv1 but not ANTXR1-sv2 associated with the actin cytoskeleton, although disruption of the cytoskeleton did not affect binding of ANTXR-sv1 to PA. Introduction of a cytoplasmic domain missense mutation found in the related receptor ANTXR2 in a patient with juvenile hyaline fibromatosis impaired actin association and increased binding of PA to ANTXR1-sv1. These results suggest that ANTXR1 has two affinity states that may be modulated by cytoplasmic signals.
Go
Mandy Y
MY
Department of Laboratory Medicine and Pathobiology, Medical Sciences Building, Rm. 6308, 1 King's College Circle, University of Toronto, Toronto, ON, Canada M5S 1A8.
Chow
Edith M C
EM
Mogridge
Jeremy
J
D019943:Amino Acid Substitution / Q000235:genetics; D000818:Animals; D000942:Antigens, Bacterial / Q000378:metabolism*; D001427:Bacterial Toxins / Q000378:metabolism*; D016466:CHO Cells; D006224:Cricetinae; D003412:Cricetulus; D016297:Mutagenesis, Site-Directed; D020125:Mutation, Missense; D011485:Protein Binding; D017434:Protein Structure, Tertiary / Q000235:genetics; D018000:Receptors, Peptide / Q000235:genetics / Q000378:metabolism*
D000942:Antigens, Bacterial; D001427:Bacterial Toxins; D018000:Receptors, Peptide; C030325:anthrax toxin; C070309:anthrax toxin receptors